The technique for reduction of the number of embryos was applied in a patient who conceived following IVF and transfer of six embryos. On the 10th week of gestation, the number of embryos was reduced from five to three by an U/S-guided intra-uterine procedure. Two healthy girls and a boy were delivered in the 36th week by cesarean section. No trace of the other two fetuses was found. The moral and technical aspects of partial preventive termination of multiple pregnancy are discussed.
A double-blind controlled study of the effects of vitamin B6 supplementation on premenstrual symptoms was conducted. Fifty-five women who reported moderate to severe premenstrual mood changes participated in the study. Symptoms were monitored prospectively through daily home record-keeping over a one-month baseline period followed by two months of treatment. Subjects were randomly assigned to receive daily supplements of 150 mg of vitamin B6 or placebo over the entire two-month treatment period. Analysis of covariance suggested that even though vitamin B6 may improve premenstrual symptoms related to autonomic reactions (eg, dizziness and vomiting) and behavioral changes (eg, poor performance and decreased social activities), a significant amount of physical and affective symptomatology remained during the premenstrual phase. In light of recently reported, potentially toxic effects of low doses of vitamin B6, our results call for caution in using this therapy for premenstrual symptoms.
Reproductive EndocrinologySpironolactone TreatmentAdrenal and OvarianAntiandrogen Therapy
Eight castrate, estrogen-replaced women were given 200 mg spironolactone daily for 4 weeks. The response of plasma dehydroepiandrosterone sulfate (DHEAS), testosterone (T), and androstenedione (delta 4A), all indicators of adrenal C19-steroid production, varied greatly among individuals. Sixteen women with idiopathic hirsutism were given night-time dexamethasone (DEX) and then superimposed spironolactone for 4 weeks, followed by DEX without spironolactone for an additional 4 weeks. As expected, DHEAS, T, and delta 4A declined on DEX treatment. On addition of spironolactone, there was little further change in DHEAS, while plasma T declined in 7 of 16 women, including all those whose T level had remained elevated despite DEX treatment; most values rebounded when spironolactone was discontinued. The authors conclude from intact DEX-suppressed women that ovarian T, especially when increased, is frequently lowered by spironolactone. Thus, both adrenal and ovarian androgen production (as measured by prevailing plasma levels) may be diminished by this agent. These highly variable effects on androgen production are unlikely to account for the consistent antiandrogenic effects reported clinically.
Among 59 laparoscopically staged endometriosis patients, 28.8% tested positive for antinuclear antibody. Of 44 patients, 45.5% were lupus anticoagulant positive (greater than 1.3) and 20.5% were within a borderline range (1.2-1.3). Antinuclear antibody positivity was inversely related to stage of disease (P = .009); lupus anticoagulant positivity exhibited a similar trend, but did not reach statistical significance. Of 31 endometriosis patients, 64.5% exhibited immunoglobulin G (IgG) autoantibodies and 45.2% demonstrated IgM autoantibodies to at least one of 16 antigens investigated. Among IgG autoantibodies, those to phospholipids were most frequently detected, followed in order of frequency by antibodies to histones and nucleotides. The incidence of IgM autoantibodies was inverted, with antinucleotides appearing most frequently and antiphospholipids least frequently. A strong correlation was noted between the presence of lupus anticoagulant and antinuclear antibody with both IgG and IgM autoantibodies. These observations suggest that endometriosis is associated with abnormal polyclonal B cell activation, a classic characteristic of autoimmune disease. This contention is further supported in that immunoglobulin levels (particularly IgG) are elevated in patients with endometriosis, and more so in lupus anticoagulant-positive than lupus anticoagulant-negative endometriosis patients (P = .021).
A double-blind, placebo-controlled, randomized multiple crossover study was designed to determine the effectiveness of alprazolam in the treatment of premenstrual syndrome. Patients maintained daily diaries of 22 premenstrual symptoms for one pretreatment control cycle and four treatment cycles. Alprazolam 0.25 mg or placebo was administered three times daily from cycle day 20 until the second day of menstruation, at which time the dosage was tapered by one tablet per day to minimize withdrawal effects. The results of the clinical trial indicate that alprazolam is significantly more effective than placebo in relieving the severity of premenstrual nervous tension, mood swings, irritability, anxiety, depression, fatigue, forgetfulness, crying, cravings for sweets, abdominal bloating, abdominal cramps, and headache. The low incidence of side effects makes alprazolam an acceptable treatment for premenstrual syndrome for those women unresponsive to other therapies.
PregnancyPremature Rupture of MembranesInflammatory BiomarkersC-Reactive Protein in Pregnancy
The value of maternal C-reactive protein (CRP) levels as predictors of fetal and maternal infective morbidity and fetal mortality was assessed prospectively over a 6-month period in all cases of premature rupture of the fetal membranes or suspected premature labour. Statistical analysis of results showed that CRP at a level of 1.32 mg/dl is a sensitive marker of infective morbidity in mother and neonate. Furthermore, there was a significant association between raised CRP levels and low-birth-weight babies, suggesting that intra-uterine infection is a major cause of prematurity in the study population.
The development of a 10-item self-report scale (EPDS) to screen for Postnatal Depression in the community is described. After extensive pilot interviews a validation study was carried out on 84 mothers using the Research Diagnostic Criteria for depressive illness obtained from Goldberg's Standardised Psychiatric Interview. The EPDS was found to have satisfactory sensitivity and specificity, and was also sensitive to change in the severity of depression over time. The scale can be completed in about 5 minutes and has a simple method of scoring. The use of the EPDS in the secondary prevention of Postnatal Depression is discussed.
Exercise is commonly listed as a remedy for the premenstrual syndrome (PMS), although no study has proven that it is an effective therapy. Numerous reports have suggested that exercise is associated with improved mood and symptoms. In those reports, however, the diagnosis of PMS was not clearly documented, nor was the exercise carefully controlled. Preliminary evidence suggests that exercise training in ovulatory, sedentary women and intensified training in women athletes decrease mild premenstrual symptoms. Although conditioning exercise is associated with short luteal phase and anovulatory cycles, decreases in mild premenstrual symptoms occur prior to menstrual cycle changes. Controlled studies of PMS and exercise training may not only document an effective, nonpharmacologic therapy for PMS but also clarify the hormonal etiology of this complex biobehavioral phenomenon.
Endometriosis has been associated with corpus luteum inadequacy and abnormalities of luteal phase progesterone (P) secretion. In this study, abnormal luteolysis, as a second factor of luteal dysfunction, was assessed in 13 women with endometriosis and 25 control patients by measurement of ovarian vein estradiol (E2) and P during the follicular phase. The results reveal that women with endometriosis have (1) significantly lower ovarian vein E2, (2) significantly higher both peripheral and ovarian vein P, and (3) threefold higher P/E2 ratios than controls during the follicular phase. These data support the concept of continued P production from an active corpus luteum well into the follicular phase of the following cycle in women with endometriosis. Failure of adequate luteolysis is a second aspect of luteal dysfunction in endometriosis and strongly supports the growing body of data confirming ovulatory asynchrony in the minimal; endometriosis infertility syndrome.
Reproductive EndocrinologyBioavailability Routes of AdministrationPharmacokineticsMicronized Progesterone
The bioavailability of micronized progesterone (P) was studied by measuring sequential serum P concentrations after a single bolus of 50-200 mg P given sublingually, orally (capsule and tablet), vaginally and rectally (suppositories) during the follicular phase in a group of normally menstruating women. When compared to other modes of P administration, the area under the curve during the first eight hours was twice as high with the rectal route. With 50 and 100 mg P given sublingually and 100 and 200 mg ingested as tablets, peak levels and area under the curve were twice as high with the higher dosage. The response was more sustained with the higher dosage. All subjects exhibited a significant increase in serum P levels over baseline that persisted for at least eight hours. P levels were still increased over baseline at 24 hours in all subjects after the administration of 100-mg vaginal and rectal suppositories and 200-mg tablets. These findings are in general agreement with previous reports showing that luteal phase serum P concentrations can be reached easily with non-parenteral modes of administering micronized P and that oral P administration could become an attractive alternative to the currently used oral mode of administering synthetic progestins.
Fertility AwarenessBiological IndicatorsSymptothermal MethodHormonal and Clinical Markers
Indirect evidence of the occurrence of ovulation, which is generally accepted, is an increase in plasma or serum progesterone. Pelvic ultrasonography can estimate the probable time of ovulation within 12 h. There is a close association between the rise in progesterone, luteinizing hormone (LH) and oestrogen peaks and ovulation. A WHO study reported that ovulation occurred at a median time of 8 h after the rise in plasma progesterone, 15 h after the LH peak and 24 h after the oestrogen peak. The basal body temperature (BBT) method is the most effective in determining the premenstrual infertile period, but it is unreliable for an accurate determination of ovulation and the postmenstrual infertile period. Nor is BBT an effective method of predicting ovulation during postpartum lactational amenorrhoea. Therefore, BBT is usually used as a secondary indicator of ovulation and is combined with more reliable indicators. Observed changes in cervical mucus patterns can be used to define the probable fertile period, although this method produces a wide range of days. The peak mucus symptom is closely correlated with ovulation. Mucus symptoms can be used as a guide for the timing of blood or urine samples for estimation of LH, oestrogen and progesterone or their metabolites. Symptothermal methods incorporate other symptoms such as cervical changes, intermenstrual pain, breast tenderness and backaches, but these are secondary signs of ovulation and are recommended to be used in conjunction with mucus and BBT.
Reproductive EndocrinologyOpioid Peptides and Metabolic FunctionDiabetes and Insulin Secretion
To address the possibility that an abnormality in pancreatic beta-endorphin activity might contribute to abnormal insulin secretion in diabetes mellitus, we studied the effects of beta-endorphin infusion on islet function in diabetic patients. The iv infusion of human beta-endorphin at a dose of 0.5 mg/h for 2 h in type-2 non-insulin-dependent diabetic patients (n = 12) raised plasma insulin and glucagon levels and slightly but significantly lowered plasma glucose concentrations. beta-Endorphin infusion also resulted in reappearance of a clear-cut acute insulin response to glucose, while second phase insulin release was increased and glucose disposal accelerated. Acute insulin and glucagon responses to arginine were not increased by beta-endorphin, suggesting that the effect of the opioid on the B cells of the diabetic patients is specific for glucose. An intraislet abnormality of opioid peptides action and/or secretion may play a role in the disturbances of insulin secretion in patients with type-2 diabetes mellitus.
Fertility AwarenessOvulation MethodAbstinence and SatisfactionNFP Effectiveness Studies
During the 13-cycle effectiveness phase of a five-center study of the ovulation method of natural family planning, there were substantial differences, particularly between the two developed and the three developing countries, in the stated degree of satisfaction with the frequency of intercourse (most couples were satisfied in Bangalore, Manila, and San Miguel, whereas one-third of the subjects and half of their partners would have preferred more frequent intercourse in Auckland and Dublin) and in expressed difficulties associated with abstinence (e.g., 62% had occasional difficulty in Auckland, 14% in Bangalore, 55% in Dublin, 28% in Manila, and 5% in San Miguel). Cumulative net probabilities of discontinuation due to pregnancy were 1.8%, 18.6%, and 54.7% for couples in whom the male partner's degree of satisfaction was described as "no difficulty," "occasional difficulty," and "always some difficulty," respectively.
A study was designed to see if the use of prophylactic progesterone vaginal suppositories (PVS) reduced the risk of spontaneous abortions in women with a history of at least one spontaneous abortion. PVS was employed during the luteal phase to the end of the first trimester. The dosage was initially 50 mg/day, but was increased according to the endometrial biopsy and doubled as soon as pregnancy was established. Only 10 women (10%) aborted, and 8 of these 10 were successful in their next PVS-treated pregnancies. Overall there were 12 losses in 132 pregnancies (9%) in these PVS-treated patients. Forty-two percent of untreated controls aborted (10/24). The results suggest that PVS is effective in reducing the risk of spontaneous abortions in high-risk patients.
Menstrual CycleExercise EffectsExercise-Induced AdaptationPhysical Training
Reproductive change during conditioning exercise (physical training provides a model of hypothalamic adaptation to alterations in the external and internal environment. Parallels exist between the reproductive changes with exercise and those occurring with physical illness, undernutrition and psychological trauma. Although menstrual cyclicity may be disrupted in younger women, luteal phase shortening, anovulation and decreased premenstrual symptoms within normal ovulatory cycles are the most frequent observations noted. Baseline LH, prolactin and oestradiol tend to be lower, and other hormones unchanged, in trained women. Testosterone may be decreased within the normal range in men. Recent evidence shows that LH pulse frequency, amplitude and area under the LH curve are decreased in both female and male runners. Interrelationships between increases in central dopamine, endorphin and probably some hypothalamic message(s) relating to nutritional state appear to modulate these reproductive changes. The clinical and therapeutic response to reproductive alterations in the context of exercise differs when these are seen as adaptive and not as disease processes (Prior and Vigna, 1985b).
Plasma beta-endorphin (beta-EP), beta-lipotropin (beta-LPH), and cortisol concentrations were measured by perimenstrual period in 11 patients affected by premenstrual syndrome (PMS) and in 8 asymptomatic healthy volunteers. Blood samples were collected every 2 to 3 days, for 1 month, starting from midcycle. The Menstrual Distress Questionnaire (MDQ) was administered during the testing period. Plasma beta-LPH and cortisol levels remain stable during the perimenstrual period, in both controls and PMS patients. On the contrary, PMS patients showed a decrease of plasma beta-EP in the week preceding menses and during the first days of menstrual flow. Beta-EP values of PMS patients regain normal levels during the next follicular phase. No changes of beta-EP levels were recorded in asymptomatic women. MDQ scores revealed that PMS patients complained of water retention, pain discomfort, and mood swings. The transient and reversible decrease of plasma beta-EP in PMS patients near to and at menses remains to be clarified.
InfertilityPregnancy ComplicationsHypertension and Gestational DiabetesComparative Outcomes by Diagnosis
We studied 500 women who conceived after investigation and treatment for different infertility problems and compared the outcome of the 5 infertility groups (Group 1 to 5), the ovulatory dysfunction (Group 1), male infertility (Group 2), A.I.D. (Group 3), tubal surgery and IVF (Group 4) and no treatment (Group 5) with the outcome in the hospital group during a period of 3 years. The incidence of abortion in Group 3 is significantly higher (13.8%), the incidence of ectopic pregnancy is significantly higher in Group 4 (21.7%) as compared with the incidence in the hospital group (P less than 0.01). The rate of pre-existing hypertension and gestational diabetes is significantly higher in all the 5 infertility groups as compared with the incidence in the hospital group (P less than 0.05). The incidence of preterm labor in general is less in the infertility group as compared with the incidence in the hospital group (P greater than 0.05). The incidence of older women, multiple pregnancy, induction of labor, operative deliveries, fetal distress, low Apgar score, babies with birth weight below the tenth centile were higher in the infertility groups (P less than 0.05). But the perinatal mortality or major or minor fetal anomalies were not significantly different in the infertility groups as compared with the rate in the hospital groups (P greater than 0.05).
Ethics/PhilosophyFeminist CritiqueTechnology and Choice
The nature and incidence of normal and abnormal spontaneous ovarian cycles, identified with ultrasound and endocrine tracking, were examined in 45 regularly cycling infertile women with no definitive cause and 15 women who were apparently normal and were receiving donor insemination because of clearly infertile partners. In 136 cycles, four apparently distinct abnormal patterns were detected. The total incidence in the infertile group was 58% compared with 23% in the donor insemination group (P less than 0.005). Twelve of 26 subjects who had at least three cycles tracked showed two different abnormalities, and 1 subject had three different abnormalities in five abnormal cycles. These results suggest that abnormal cycles are a significant factor in unexplained infertility and that diagnosis and treatment cannot be based on the study of a single cycle.
InfertilityLuteinized Unruptured Follicle SyndromeLimitations of Traditional MethodsLUF Syndrome
The luteinized unruptured follicle syndrome is a form of anovulation and a subtle cause of female infertility. The syndrome cannot be diagnosed by traditional progesterone-dependent ovulation detection methods. Without the use of invasive procedures or sophisticated equipment, the luteinized unruptured follicle syndrome may go unnoticed. The patient diagnosed as ovulatory, on the basis of traditional ovulation detection methods, who does not conceive may be experiencing the luteinized unruptured follicle syndrome, and thus infertility. The syndrome's incidence, detection, etiology, and treatment are described.
Six months of exercise training was associated with decreased premenstrual symptoms in two groups of women. There was no change in symptoms in nontraining women. Eight sedentary (ST) women increased running from 0 to 76 +/- 26 km/cycle (mean +/- standard deviation) over 6 months and seven runners (MT) trained for a marathon (42.2 km). Six normally active, nontraining (C-NT) women kept their activity constant. Each subject completed monthly intensity-graded questionnaires or kept daily symptoms diaries concerning premenstrual symptoms. All monitored basal body temperature, weight, and exercise. Gonadal steroids were measured in ST women. For ST subjects, breast (P = 0.005), fluid (P = 0.01), and personal stress (P = 0.025) decreased. MT women experienced decreased fluid (P = 0.034) and depression (P = 0.014). Anxiety tended to decrease (P = 0.087). ST and MT subjects experienced decreases in premenstrual symptoms without documented hormonal, menstrual cycle, or weight changes. These symptom changes appear to be the earliest evidence of the effects of conditioning exercise on the reproductive system.
Controversy still exists as to the proper therapy of luteal phase defects. Some advocate using drugs to improve follicular dynamics, e.g., clomiphene citrate, while others treat luteal phase defects with progesterone. The possibility exists that in some cases the luteal phase defect is secondary to failure to produce a mature follicle, the better drug then being an ovulation-inducing drug, e.g., clomiphene. However, if the follicle is mature, then progesterone may be the best treatment. We defined mature follicle as one between 18 and 24 mm while the serum estradiol (E2) level is over 200 pg/mL. The efficacy of exclusive P therapy was evaluated in 50 women, all with a minimum of 1 1/2 years infertility and with no obvious fertility problems other than luteal phase defect. Seventy percent of the women conceived within 6 months. The abortion rate was 14.7%. The average period of infertility was 2.8 years in the 35 patients who conceived within 6 months. These data suggest that determining the degree of follicular maturation by serum E2 and pelvic sonography plus excluding the luteinized unruptured follicle syndrome by pelvic sonography helps determine the proper therapy for luteal phase defect.
Cervical incompetence is one of the main contributors to repeated pregnancy loss, accounting for approximately 25% of the cases. Typically it results in progressive cervical dilatation, leading to a painless second- or early-third-trimester abortion. In most instances cervical incompetence is the result of previous obstetric or gynecologic trauma; a congenital etiology is unusual. Despite the various reported diagnostic procedures, the obstetric history and frequent visual and digital examinations during pregnancy remain the most important factors in arriving at the correct diagnosis. In spite of the fact that numerous procedures have been advocated as treatment, the McDonald purse string closure technique is by far the most simple and effective corrective surgical technique, yielding an overwhelming number of successful pregnancies.
We have previously shown that prophylactic supplementation of progesterone beginning in the luteal phase of patients treated with human menopausal gonadotropins (hMG) could reduce the risk of spontaneous abortions. The present study was initiated with 100 patients to evaluate the efficacy of a new progesterone therapeutic regime in patients requiring either hMG or clomiphene citrate. A significantly decreased risk of spontaneous abortion (6% vs. 28%) was seen in 50 patients prophylactically treated with progesterone as compared with 50 control patients. The progesterone regimen was then tried on 566 consecutive patients who were treated and conceived with hMG or clomiphene citrate, and approximately the same risk (6.2% by 20 weeks) was found. This incidence of spontaneous abortion is even less than the accepted risk for the general population.
PCOSOpiate Receptor BlockadeHyperinsulinemia and Insulin ResistanceMetabolic Effects
We previously reported that circulating beta-endorphin levels are increased in obese hirsute women and that plasma immunoreactive insulin (IRI) levels are increased in proportion to the degree of hyperandrogenism in women with the polycystic ovary (PCO) syndrome. We, therefore, tested the hypothesis that endogenous opiates are at least partially responsible for the hyperinsulinemia and insulin resistance in this syndrome. In the first study, acute naloxone administration significantly reduced the plasma IRI response and IRI/glucose ratio in three euglycemic obese women with PCO and acanthosis nigricans (AN) and marked insulin resistance, but did not alter the glucose response. Naloxone had no effect on these parameters in the normal weight control subjects. In the second study, nalmefene, a new, orally active opiate antagonist, reduced IRI and the IRI/glucose ratio in four women with PCO-AN and marked hyperinsulinemia in a randomized, double blind, crossover protocol. We conclude that endogenous opiates are at least partially responsible for the hyperinsulinemia and insulin resistance in PCO-AN.
C-reactive protein has been used to identify patients at high risk for infectious morbidity with preterm labor or preterm rupture of membranes. In this article we report on 104 patients with preterm labor symptoms (n = 45) or preterm rupture of the membranes (n = 59) and serial evaluations of C-reactive protein measured by latex agglutination and laser nephelometry. The simple, inexpensive latex method appears comparable to the laser method in predicting infectious morbidity and can be used clinically. Elevated C-reactive protein values before delivery predict infectious morbidity in only 8% to 29% of patients, and up to 18% of patients with serious infections may be misdiagnosed as having normal C-reactive protein values before delivery.
Men with PRL-producing macroadenomas often present with hypogonadism and impotence. This report documents exacerbation of a PRL-secreting tumor after two separate 200-mg testosterone enanthate (T) injections despite continued bromocriptine (BRC) therapy. A 37-yr-old man with a 60-mm invasive tumor and a serum PRL level of 13,969 +/- 332 ng/ml (mean +/- SD) responded to BRC therapy with rapid disappearance of visual field defect, headache, and facial pain as well as decrease in serum PRL to 5,103 +/- 1,446 ng/ml. T injection was followed by severe headache, facial pain, and increase in PRL to 13,471 ng/ml. Visual field deterioration and increased tumor size (height, 40-43 mm) by computed tomography were documented. A relationship between T injection and exacerbation of the prolactinoma was not recognized until after a second T injection 3 months later. After that therapy, baseline PRL increased from 6,900 to 12,995 ng/ml. The hypothesis that T was aromatized to estradiol, directly stimulating lactotrophs, was supported by an increase in serum estradiol from 24 to 51 pg/ml after the second T injection. Although T treatment is accepted as appropriate therapy for hypogonadism in men with prolactinomas, it may not only interfere with the response of the tumor to BRC therapy, but even stimulate tumor growth and secretion.
EndometriosisPelvic Distribution by AgeDisease Progression PatternsEndometriosis and Fertility
In this series of patients, endometriosis does not involve more pelvic areas in older age groups. Exposure to pregnancy is associated with slightly less pelvic involvement, although this effect is inconstant when age groups are studied individually.
Fertility AwarenessSimplified Teaching MethodsLife Table AnalysisDeveloping Country Application
Researchers used life table rates from study and comparison groups from rural and urban areas of Cagayan de Oro City, the Philippines to test a simplified method of teaching natural family planning (NFP) defined by calendar, mucus, and cervix indicators. This method included a 6 page booklet, 2 30-minute training sessions, and a question and answer period. Fear of side effects from other contraceptive methods was the leading reason for using NFP (79.4% urban, 85.8% rural). Religious motivation and fear of side effects followed for urban couples, but the percentage was low (14.6%). In rural areas, religious motivation place 3rd (4.1%) preceded by other reasons (6.9%). User error resulted in low accidental pregnancy rates (.8%). Method failure was responsible for higher failure rates than user error, but they were still relatively low (3.4% total). In rural areas, the reason for failure was unclear in 2.6% of couples, but it was only .9% among urban couples. Rural couples who used NFP to space births (spacers) had 2 times the failure rate of those rural couples who used NFP to limit births (limiters) [69% vs. 31%]. Urban spacers had a higher failure rate than urban limiters, but the difference was smaller than it was for rural couples (54.8% vs. 45.2%). Lactation did not have a clear effect on failure rates. For example, in urban areas, partially lactating women had a lower failure rate than nonlactating women (41.9% vs. 58.1%), but in rural areas, lactation had the opposite effect (63.6% for lactating women and 36.4% for nonlactating women). Risk taking resulted in more 6 month pregnancy rates among urban couples than rural couples (12.3% vs. 8.2%). At the end of 6 months, 67.5% of all couples still used the new simplified NFP method (70.3% rural vs. 64.7% urban). Therefore the new simplified NFP method was an effective method for spacing or limiting births.
InfertilityCervical Mucus DeficiencyEstrogen Receptor AssessmentEndocervical Gland Function
Endocervical gland estrogen receptor (ER) deficiency has been proposed as a possible cause for the poor cervical mucus (CM) in some infertile women with cervical factor. Cytosol ERs were measured in endocervical tissue obtained by biopsy within 3 days of ovulation (determined by the endogenous luteinizing hormone [LH] surge) in five infertile women with persistent poor preovulatory CM (group 1) and in endocervical tissue obtained in the late follicular phase in eight ovulatory women with excellent CM (group 2). ER concentrations were measured in Fmol/mg protein by the dextran-coated charcoal separation method (New England Nuclear Kit, Boston, MA). CM score evaluation and measurement of serum estradiol (E2) and progesterone (P) levels were performed concomitantly. Serum E2 levels of 123.4 +/- 29.3 pg/ml (mean +/- standard error of the mean [SEM]) in group 1 were comparable to E2 levels of 123.3 +/- 15.0 pg/ml in group 2. Serum P concentrations of 0.9 +/- 0.27 ng/ml in group 1 were comparable to 0.79 +/- 0.29 in group 2. A CM score of 4.6 +/- 0.69 in group 1 was significantly lower than 11.6 +/- 0.53 in group 2 (P less than 0.01). The cytosol ER was negative in four of five women in group 1, whereas in group 2, ER was positive in six, borderline in one, and negative in one subject. This study suggests that cytosol ER may be deficient in some women with cervical factor.
Body LiteracyAdolescent ProgramsOvulation MethodAdolescent Outcomes
Fertility awareness is experiential learning about cyclic fertility. This awareness, used as a family planning method, differs from contraception because it does not isolate the procreative capacity of either partner. The acceptability and effect of teaching fertility awareness on teen sexual activity and decision making was tested in a multisite pilot program which taught fertility awareness via the prospective marker of the cervical mucus (ovulation method of natural family planning). 200 US and 35 Guatemalan volunteer women ages 15-17 in a structured 1 year curriculum, monitored cycle charting and explored the implications of experiencing one's signs of fertility. Control subjects were recruited from the general population and from family planning clinics. 9% of the US study group were sexually active prior to entry. By cycle 12, 1/2 had discontinued activity. Conception rate was 0.0044. The continuation rate dropped from 90% at cycle 7 to 71% at cycle 8 due to scheduling constraints for 2 classes and to 57% at cycle 12. Postprogram follow-up of early leavers showed only 1/3 the expected rate of onset of sexual activity and pregnancy. Parent involvement correlated positively with postponement and/or discontinuation of sexual activity. Reported movement away from peer group pressure appeared 3 months after entry.
Research MethodologyLipid Drug Delivery SystemsIntestinal Lymphatic Absorption
The lipoprotein fractions in mesenteric lymph were monitored following intraduodenal administration of arachis oil and oleic, linoleic and linolenic fatty acids to rats. An increase in the chylomicron fraction, but not the VLDL or LDL fraction, was observed with each lipid. The greater the degree of unsaturation of the fatty acid, the more rapid the onset of chylomicron synthesis. The administration of linoleic acid and arachis oil produced the highest concentration of chylomicrons in the lymph. These results reflect differences in the rate of absorption and biochemical metabolism of the lipids and have implications for the selection of vehicles for the delivery of drugs by the lymphatic route.
Body LiteracyNFP Training ProgramsProgram EvaluationPractitioner Training
Fisher JC, 1987·Journal of Clinical Laser Medicine & Surgery
In the past 32 years, lasers have progressed from interesting curiosities to important instruments in medicine and surgery, with a wide variety of wavelengths and medical-surgical applications. Today's physician is faced with a bewildering array of laser types, each touted by its manufacturer as the ultimate surgical tool. This article sets forth in simple, understandable prose, the basic principles of the interaction of laser light with living tissue, so that the physician can decide which type of laser is best suited to a given application, without relying on the manufacturer's sales literature. The topics discussed are the nature of light; reflection, absorption, scattering, and attenuation in living tissue; physical processes by which laser light destroys tissue; relative importance of the three unique properties of laser light in surgery and therapy; temporal modes of lasers; means of delivering laser beams to their targets; and considerations in the selection of laser systems.
Gerhard I et al., 1987·Biol Res Pregnancy Perinatol
Between 1983 and 1984 a double-blind randomized study with progesterone substitution in threatened abortion was carried out. Fifty-six patients with vaginal bleeding during the first trimester of pregnancy, the internal cervical os being closed, were referred to the hospital. Twenty-five women (5th and 6th week of gestation) with positive serum concentrations of beta-hCG were admitted to the study without regard to sonogram results. In other 25 women (7th-10th week of pregnancy) and 6 women (greater than or equal to 11th week of pregnancy) fetal heart action and movement could be demonstrated by ultrasound. The patients were prescribed bed rest and vaginal suppositories twice daily, containing either 25 mg progesterone or only polyethylene glycol. The code was not broken until after completion of the study. Serial serum determinations of beta-hCG, estradiol-17 beta (E2), progesterone, and ultrasound were performed. Four patients had to be omitted from final analysis (two tubal pregnancies, one intrauterine infection, one sectio parva). Three of 26 patients progesterone (11%) and five of 26 patients with placebo (19%) had an abortion, which represented no significant difference. Frequency of abortion was increased in women more than 30 years old, in women with previous abortions and after ovulation induction. Progesterone treatment resulted in a significant elevation of serum progesterone concentrations (p less than 0.01), while beta-hCG and E2 were unchanged. The results of this study confirm that pregnancy outcome is favorable in women with bleeding and normal hormone concentrations without hormonal treatment and unfavorable in women with reduced beta-hCG and E2-concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
This paper presents the main survey findings from a nationally representative sample of 607 users of periodic abstinence methods in the Philippines in 1984. The survey was conducted because of the widespread popularity of periodic abstinence in the Philippines and a lack of detailed knowledge about how the method is understood and practiced in the Philippines. Findings are presented on the prevalence of the different types of periodic abstinence methods, the nature of their use, knowledge about the various periodic abstinence methods, instruction received, perceived advantages and disadvantages, the husband's role, and the use-effectiveness of periodic abstinence both with and without backup methods. The implications of these findings for program management and for future research are also discussed.
Reproductive EndocrinologyGnRH PulsatilityRegulation of SecretionGnRH Pulse Generator
Reproductive function in humans changes markedly during life and is usually divided into four stages. During the initial stage, which begins early in fetal life and ends in infancy, gonadotropins and gonadal steroids are secreted at levels similar to those seen in early and mid-adolescence. In the second stage, which lasts from infancy through the first decade of life, reproductive function first regresses and then becomes quiescent. Puberty, the third stage, is heralded by a nocturnal increase in the secretion of gonadotropins and sex steroids. This nocturnal predominance gradually diminishes and disappears during the fourth stage — adulthood. In men, . . .
Examples of a combined approach using in vivo as well as in vitro methods for the assessment of prenatal toxicity are presented. The topics discussed include the analysis of the possible embryotoxic potential of valproic acid (VPA), female sex hormones, bis(tri-n-butyltin) oxide (TBTO), and acyclovir and the problem of supplementing in vitro systems with drug-metabolizing activity.
High-volume intravenous urography was performed in 63 women with surgically proven endometriosis. Subtle abnormalities were found in 15.9% of these women. No patient had urologic symptoms, and there was no evidence of hydroureter or ureteral obstruction on the IVP. Long-term follow-up study will be required to determine whether or not these lesions will progress and cause ureteral obstruction.
Effective tocolytic therapy depends on the ability to make an early diagnosis of preterm labor. This study was designed to assess whether daily ambulatory home monitoring of uterine activity could facilitate early diagnosis of preterm labor. Of 76 patients at high risk for preterm labor who used daily ambulatory tocodynamometry, approximately half developed preterm labor. Evaluation when the diagnosis of preterm labor was first established has shown that in 8% of the patients the cervix was dilated more than 2 cm, shortened to less than 0.5 cm in 23%, and the fetal membranes were intact in all subjects. The same evaluation in 76 nonrandom contemporary controls matched for risk factors, maternal age, and parity has shown that more than 50% had a cervix dilated more than 2 cm, 38% had a cervix shorter than 0.5 cm, and 24% had rupture of the fetal membranes. Ultimately, 88% of the monitored patients and 59% of controls delivered at term. Comparisons between these groups indicate that intermittent home tocodynamometry may indeed be useful in making the early diagnosis of preterm labor.
Four patients who had no oocytes retrieved during an IVF cycle were studied in an attempt to identify predictors of such an occurrence and suggestions for its cause. All 30 follicles aspirated in five cycles in these four women yielded no oocytes. One patient had two cycles that produced no eggs. The empty follicle syndrome may represent a new syndrome and a cause of infertility.
EndometriosisRetrograde MenstruationPeritoneal Fluid AnalysisConsecutive Case Series
Peritoneal fluid (PF) was studied for the presence of endometrial tissue in a consecutive series of 67 women (with documented tubal patency) undergoing diagnostic laparoscopy, tubal lavage, and hysteroscopy. PF was completely aspirated from the cul-de-sac both before and after uterine irrigation. The PF was then analyzed for the presence of endometrial tissue. In native PF no significant difference in the incidence of endometrial tissue between patients with (19%) and without (11%) endometriosis (P = 0.6) was observed. Refluxed PF, obtained after uterine irrigation, showed a significantly higher incidence of endometrial tissue in women with endometriosis (76%) as compared to controls (42%) (P = 0.03). We propose two models to explain the development of endometriosis. These are not mutually exclusive, may be independent of each other, and may represent two distinct pathophysiologic disease processes.
InfertilityFollicular Development AbnormalitiesFollicular Growth AssessmentLH Surge Abnormalities
A prospective study of six unselected couples diagnosed as having unexplained infertility was done. In three of six patients, subtle abnormalities in follicular development were detected. In the first case poor follicular growth was observed. There was a premature small rise of luteinizing hormone (LH) with subsequent low levels of estradiol (E2) in the late follicular phase and unusual wide LH peak. This was followed by low progesterone levels in the luteal phase. In the second case follicular growth was abrupted by premature LH surge. This surge was triggered by early rise of E2 level while the follicle was still small in size. In the third case luteinized unruptured follicle syndrome was diagnosed, on ultrasound examination. All of the abnormalities were repetitive.
EndometriosisLUF SyndromeDanazol and Ovulation InductionEndometriosis Cases
The effectiveness of ovulation induction with clomiphene citrate or human menopausal gonadotropins was evaluated in 52 infertile women with stage I or stage II endometriosis anovulation or luteinized unruptured follicle (LUF) syndrome before (group I) and after (group II) danazol treatment. The incidence of anovulation and LUF in the endometriosis population was 9% and 34%, respectively. In group I, 10 of 36 patients (27.8%) conceived, with an average of 17.6 induction cycles per pregnancy. In group II, 21 of 30 patients (70%) conceived, with an average of 4.5 cycles per pregnancy (difference significant at P less than 0.001). There was no difference in the average number of ovulation induction cycles per patient between groups I and II (4.9 and 3.1, respectively). Of 14 patients who did not conceive in group I and crossed over to group II, 9 (64.3%) conceived (not different from group II). Spontaneous abortion rates were 20% in group I and 14% in group II. These results indicate that mild endometriosis may interfere with conception through mechanisms other than ovulatory dysfunction and that treatment with danazol appears to more than double the fertility rate.
Two hundred seventy-four infertile patients and 43 women with two or more previous first-trimester abortions underwent a luteal function evaluation by basal body temperature, plasma progesterone, estradiol and prolactin determination, and endometrial biopsy (repeated in a later cycle when the first was defective). An endometrial luteal phase deficiency was detected in 37 (13.5%) of the infertility cases and in 14 (32.5%) of the patients with recurrent miscarriage. However, the endometrial defect was associated with normal hormonal levels in the great majority of patients (86.3%).
There has been an increase in interest in natural family planning (NFP) in recent years. The Roman Catholic Church and other groups sympathetic to NFP philosophy have pressured the US Agency for International Development (AID) to increase emphasis on NFP, and AID has responded by increasing funding devoted to NFP from US$0.8 to US$7.8 million from 1981-85. In 1985, AID exempted NFP providers from the requirement of providing direct or referral services for other methods, but repealed the exemption in 1986. Several methods rhythm, the estimation of ovulation time by the counting of days elapsed in relation to menstruation; and the more precise cervical musus; basal body temperature; and sympto-thermal methods. Because NFP requires considerable training, recording, and willingness to abstain, recruitment is difficult and dropout rates high. A 5-country World Health Organization study found that 17% of women dropped out during training, and 36% discontinued during the following year. At the 4th International Congress of the International Federation for Family Life Promotion (IFFLP), it was stressed that data on NFP prevalence classed by type of NFP are lacking. Questions raised included whether populations of countries that have achieved or hope to achieve a low birth rate will be interested in NFP; whether NFP can increase the risks of birth defects through fertilization by "aged gametes;" and whether NFP is capable of helping couples to select the sex of the child. The implications of the contraceptive effects of breastfeeding were reviewed. Some problems arise concerning NFP advocates often do not consider couples who "break the rules" as acceptors, and when these couples are excluded from data the method appears much more effective. Traditionalists emphasize the increased quality that NFP brings to a marital relationship. Some participants maintained that rigid moral advocacy would deter many couples.
Factors influencing the probability of conception after artificial insemination with donor semen were investigated in a series of 80 infertile couples. Overall, 46 pregnancies were achieved for a crude pregnancy rate of 58%. Life table analysis showed a cumulative probability of conception of 97.1% at the end of 12 cycles and an average fecundability of 15.1%. These results were achieved using a single insemination per cycle and individualizing the day of insemination based on the woman's basal body temperature. Women who had been pregnant previously had a significantly better fecundability than nulligravid women (P less than .05). The overall rates of conception in those women who required therapy for ovulatory dysfunction were the same as normal women although the fecundability was somewhat lower. Women who had abdominal pathology had an overall conception rate of 23%.
Data on 575 couples undergoing 1057 consecutive cycles of in vitro fertilization (IVF) were used to calculate cumulative pregnancy rates for repeated IVF cycles. Excluding preclinical abortions and couples in whom the male partner had poor semen parameters, calculated cumulative pregnancy rates for cycles 1 to 6 were 13.6%, 24.8%, 37.2%, 47.8%, 52.2%, and 59.6%, respectively. A parametric model used to fit these data yielded a strong correlation between observed and predicted pregnancy rates (r = 0.99, P less than 0.001). Predicted cumulative pregnancy rates after 9 and 12 cycles were 75% and 84%, respectively. Excluding preclinical abortions, the pregnancy rate per cycle was approximately constant, at approximately 15% over repeated cycles. As the cost of IVF declines and as treatment cycles become more easily tolerated, persistence in IVF can lead to successful pregnancy for a large proportion of couples.
General OB/GYNElectronic Fetal MonitoringFetal Monitoring StrategiesProspective Comparative Studies
We investigated the effects of using intrapartum electronic fetal monitoring in all pregnancies, as compared with using it only in cases in which the fetus is judged to be at high risk. Predominant risk factors included oxytocin stimulation of labor, dysfunctional labor, abnormal fetal heart rate, or meconium-stained amniotic fluid. This prospective alternate-month clinical trial took place over a 36-month period during which 34,995 women gave birth. In alternate months, either 7 (for "selective monitoring") or 19 (for "universal monitoring") fetal monitors were made available in the labor and delivery unit. During the "selective" months, 6420 of 17,409 women (37 percent) were electronically monitored, as compared with 13,956 of 17,586 women (79 percent) during the "universal months." Universal monitoring was associated with a small but significant increase in the incidence of delivery by cesarean section because of fetal distress, but perinatal outcomes as assessed by intrapartum stillbirths, low Apgar scores, a need for assisted ventilation of the newborn, admission to the intensive care nursery, or neonatal seizures were not significantly different. We conclude that not all pregnancies, and particularly not those considered at low risk of perinatal complications, need continuous electronic fetal monitoring during labor.